Difference in Dachsous Levels between Migrating Cells Coordinates the Direction of Collective Cell Migration

Arata, Masaki; Sugimura, Kaoru; Uemura, Tadashi

doi:10.1016/j.devcel.2017.08.001

Cited by 25 publications

(22 citation statements)

References 123 publications

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“…Originally predicted to be at the A/P compartment border ( Casal et al, 2002 ) we conclude now that a Ds peak occurs two cells in front of that border, in row 10 (Figure 9; a similar peak two cells from the A/P border has been described in the dorsal abdomen of the pupa Arata et al, 2017 ). This observation is supported by both D localisation and the orientation of ectopic denticles formed by ovo -expressing clones.…”

Section: Discussionsupporting

confidence: 66%

“…We proposed that the levels of Ds activity would be graded in opposite ways in the A and the P compartment and ultimately these gradients would be read out as PCP in each of the cells ( Casal et al, 2002 ). We imagined that gradients of Ds activity would persist and this has been assumed by most ( Casal et al, 2006; Matis and Axelrod, 2013; Lawrence and Casal, 2018; Fulford and McNeill, 2019 ) and actually detected, locally, in the migrating larval epidermal cells in the pupa ( Arata et al, 2017 ). Alternatively, once the arrow of polarity has been established in each cell, a redistribution of bridges could occur and ultimately each cell would develop the same numbers and disposition of bridges and, if so, no persistent multicellular gradient in Ds amounts would be present (eg Hale et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

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Planar cell polarity in the larval epidermis ofDrosophilaand the role of microtubules

Pietra

Lawrence

et al. 2020

Preprint

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10We investigate the mechanisms of planar cell polarity (PCP) in the larval epidermis of 11 Drosophila. Measurements of the amount of Dachsous across the segment find a peak 12 located near the rear of the anterior compartment. Localisation of Dachs and 13 orientation of ectopic denticles reveal the polarity of every cell in the segment. We 14 discuss how well these findings evidence a zigzag gradient model of Dachsous activity. 15 Several groups have proposed that Dachsous and Fat fix the direction of PCP via 16 oriented microtubules that transport PCP proteins to one side of the cell. We test this 17 proposition in the larval cells and find that most microtubules grow perpendicularly 18 to the axis of PCP. We find no significant bias in the polarity of those microtubules 19 aligned close to that axis. We also reexamine published data from the pupal abdomen 20 and fail to find evidence supporting the hypothesis that microtubular orientation 21 draws the arrow of PCP. 22As cells construct embryos and organs they need access to vectorial information that 24 informs them, for example, which way to migrate, divide, extend axons or how to 25 orient protrusions. In Drosophila there are (at least) two conserved genetic systems 26 Page 2 of 32 that generate vectorial information, and here we are concerned with only one of those, 27 the Dachsous/Fat system. Dachsous (Ds) and Fat (Ft) are large atypical cadherin 28 molecules that form heterodimeric bridges from cell to cell that help build planar cell 29 polarity (PCP) in one cell and also convey polarity between cells (Ma et al., 2003; 30 Matakatsu and Blair, 2004; Casal et al., 2006; Lawrence and Casal, 2018). The 31 activity of Ft is increased and Ds is reduced when they are phosphorylated by a third 32 molecule, Four-jointed (Fj), a Golgi-based kinase (Ishikawa et al., 2008; Brittle et al., 33 2010; Simon et al., 2010). The distribution of Ds, Ft and Fj and the interaction 34 between these molecules together determine what we describe as "Ds activity", by 35 which we mean the propensity of Ds on one cell to bind to Ft in the neighbouring cell. 36 Experiments suggest that, using the disposition and orientation of Ds-Ft bridges, each 37 cell compares the Ds activity of its two neighbours and points its denticles towards the 38 neighbour with the higher Ds activity. In this way, the local slopes in a landscape of Ds 39 activity determine polarities of all the cells (Casal et al., 2002; see Lawrence and 40 Casal, 2018 for more explanation). 41 A model: the ventral epidermis of the Drosophila larva 42Each segment of the larva is divided by cell lineage into an anterior (A) and a 43 posterior (P) compartment. In the ventral epidermis, a limited region of the segment 44 makes rows of thorny denticles that are polarised in an almost invariant pattern, while 45 the larger part of each segment makes no denticles and therefore its polarity is not 46 known (Figure 1-figure supplement 1). The Ds/Ft system is alone effective in 47 48 the "core" or Stan/Fz system (Casal et ...

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Planar cell polarity in the larval epidermis ofDrosophilaand the role of microtubules

Pietra

Lawrence

et al. 2020

Preprint

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“…During their expansion, histoblasts do not confront a free space but a well-defined larval epithelium. Along this process, LECs do not behave as passive element and they actively delaminate as the epithelial nests grow (Ninov et al, 2007(Ninov et al, , 2010Nakajima et al, 2011;Bischoff, 2012;Arata et al, 2017;Teng et al, 2017). Delamination, to avoid any type of transient or permanent gap in the epithelium, is coordinated with the expansion of the nests, and our data indicate that the initial pressure imposed by the proliferation of histoblasts is mechanically transmitted to the LECs.…”

Section: Mechanical Coupling Of Growth and Deathmentioning

confidence: 76%

Mechanical coordination is sufficient to promote tissue replacement during metamorphosis in Drosophila

et al. 2019

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During development, cells coordinate to organize in coherent structures. Although it is now well established that physical forces are essential for implementing this coordination, the instructive roles of mechanical inputs are not clear. Here, we show that the replacement of the larval epithelia by the adult one in Drosophila demands the coordinated exchange of mechanical signals between two cell types, the histoblasts (adult precursors) organized in nests and the surrounding larval epidermal cells (LECs). An increasing stress gradient develops from the center of the nests toward the LECs as a result of the forces generated by histoblasts as they proliferate and by the LECs as they delaminate (push/pull coordination). This asymmetric radial coordination of expansive and contractile activities contributes to epithelial replacement. Our analyses support a model in which cell-cell mechanical communication is sufficient for the rearrangements that implement epithelial morphogenesis.

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“…Fat1 belongs to the family of Fat-like atypical cadherins [15]. Together with their partner cadherins Dachsous, Fat-like cadherins are involved in regulating coordinated cell behaviors such as planar cell polarity in epithelia [15][16][17], collective/polarized cell migration [18][19][20], and oriented cell divisions [21,22].…”

Section: Introductionmentioning

confidence: 99%

Tissue-specific activities of the Fat1 cadherin cooperate to control neuromuscular morphogenesis

Helmbacher

2017

Preprint

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Muscle morphogenesis is tightly coupled with that of motor neurons (MNs). Both MNs and muscle progenitors simultaneously explore the surrounding tissues while exchanging reciprocal signals to tune their behaviors. We previously identified the Fat1 cadherin as a regulator of muscle morphogenesis, and showed that it is required in the myogenic lineage to control the polarity of progenitor migration. To expand our knowledge on how Fat1 exerts its tissue-morphogenesis regulator activity, we dissected its functions by tissuespecific genetic ablation. An emblematic example of muscle under such morphogenetic control is the cutaneous maximus (CM) muscle, a flat subcutaneous muscle in which progenitor migration is physically separated from the process of myogenic differentiation, but tightly associated with elongating axons of its partner motor neurons. Here, we show that constitutive Fat1 disruption interferes with expansion and differentiation of the CM muscle, with its motor innervation and with specification of its associated MN pool.Fat1 is expressed in muscle progenitors, in associated mesenchymal cells, and in MN subsets including the CM-innervating pool. We identify mesenchyme-derived connective tissue as a cell type in which Fat1 activity is required for the non-cell-autonomous control of CM muscle progenitor spreading, myogenic differentiation, motor innervation, and for motor pool specification. In parallel, Fat1 is required in MNs to promote their axonal growth and specification, indirectly influencing muscle progenitor progression. These results illustrate how Fat1 coordinates the coupling of muscular and neuronal morphogenesis by playing distinct but complementary actions in several cell types. Author summaryBuilding neuromuscular circuits involves a tight control of morphogenetic and regulatory events driving muscle and motor neuron development. Alterations of these processes can lead to congenital abnormalities or be at the root of human pathologies. Here, we show that the mouse Fat1 cadherin gene, a developmental regulator of muscle morphogenesis, coordinates the coupling between muscle and neuronal development by playing complementary functions in mesenchyme, muscles and motor neurons. These findings may be particularly relevant for Facioscapulohumeral dystrophy (FSHD), a muscle disease affecting subgroups of muscles in the face and shoulder, which is thought to involve developmental alterations. Although FSHD is known to traditionally result from a complex combination of genetic defects, the link between the altered molecular mechanisms and the specific set of muscles affected in patients is still poorly understood. Fat1 deficiency in mice causes phenotypes reminiscent of FSHD symptoms. Furthermore, pathogenic FAT1 variants have been identified in patients with FSHD-like phenotypes, and FAT1 expression is deregulated in classical forms of FSHD. Thus, a better understanding of the developmental functions of Fat1 could guide research on FSHD pathogenesis. In particular, by showing that Fat1 disru...

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Difference in Dachsous Levels between Migrating Cells Coordinates the Direction of Collective Cell Migration

Cited by 25 publications

References 123 publications

Planar cell polarity in the larval epidermis ofDrosophilaand the role of microtubules

Planar cell polarity in the larval epidermis ofDrosophilaand the role of microtubules

Mechanical coordination is sufficient to promote tissue replacement during metamorphosis in Drosophila

Tissue-specific activities of the Fat1 cadherin cooperate to control neuromuscular morphogenesis

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